辛伐他汀改善.pptVIP

Making Zocor a better drug 2015年12月9日 Contents 1.Basic information 2. Physicochemical properties 3. Development history Indications 4. Intracorporal process Adverse reactions 5.Mechanism of Action 6.Synthetic route QSAR 7. Making Zocor a better drug Basic information Trade name : Zocor Active substance：simvastatin Developed by Merck in 1988 , the second statins in the world , methylized derivatives of lovastatin in side chains Launched in Sweden in 1988，approved by US FDA in 1991. Physicochemical properties White crystalline powder ，odourless。Easily dissolved in ethanol ,acetone and acetonitrile , practically insoluble in water。melting point： 135～138℃。Need to be kept in dark place Development history lovastatin simvastatin Activity: twice as strong as lovastatin But much higher risk of rhabdomyolysis methylation Indications 1, hyperlipidaemia 2, coronary heart disease , congestive heart failure and angina 3, complications of diabetes mellitus type 2 4, preventing atherosclerosis the first choice of hyperlipidemia patients with high cholesterol Intracorporal process A prodrug with no activity until lactonic ring is hydrolyzed to a open chain hydroxy-acid derivatives in vivo 1.Absorption，distribution and metabolism: mostly in the liver ; excretion: bile excretion 2.Strong first-pass elimination and low bioavailability 3. Extensive drug interactions Adverse reactions 1, rhabdomyolysis and myodynia (the common ADR of all statins, especially in combined pharmacotherapy with fibrates and amiodarone，mechanism hasn’t been clear yet) FDA has warned of the risk of serious muscle damage of simvastatin 2, urinary system : diuresis 3, lupus-like symptomes 4, memory impairment rhabdomyolysis and myodynia Symptom：pain , tenderness , swelling and weakness of